Mechanisms of Actinidia chinensis Planch in treating colon cancer based on the integration of network pharmacology, molecular docking, and experimental verification.

BACKGROUND: As an anticancer Chinese herbal medicine, the effective components and mechanism of Actinidia chinensis Planch (ACP, Tengligen) in the treatment of colon cancer are still unclear. In the present study, the integration of network pharmacology, molecular docking, and cell experiments was employed to study the effective mechanism of ACP against colon cancer. METHODS: The Venn diagram and STRING database were used to construct the protein-protein interaction network (PPI) of ACP-colon cancer, and further topological analysis was used to obtain the key target genes of ACP in colon cancer. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to visualize the related functions and pathways. Molecular docking between key targets and compounds was determined using software such as AutoDockTools. Finally, the effect of ACP on CT26 cells was observed in vitro. RESULTS: The study identified 40 ACP-colon key targets, including CASP3, CDK2, GSK3B, and PIK3R1. GO and KEGG enrichment analyses found that these genes were involved in 211 biological processes and 92 pathways, among which pathways in cancer, PI3K-Akt, p53, and cell cycle might be the main pathways of ACP against colon cancer. Molecular docking verified that the key components of ACP could stably bind to the corresponding targets. The experimental results showed that ACP could inhibit proliferation, induce apoptosis, and downregulate the phosphorylation of PIK3R1, Akt, and GSK3B in CT26 cells. CONCLUSION: ACP is an anti-colon cancer herb with multiple components, and involvement of multiple target genes and signaling pathways. ACP can significantly inhibit proliferation and induce apoptosis of colon cancer cells, which may be closely related to the regulation of PI3K/AKT/GSK3B signal transduction.

Exploring the anticancer potential of Actinidia chinensis Planch root extracts (acRoots) on hepatocellular carcinoma: A molecular mechanism study.

Hepatocellular carcinoma (HCC), ranking as the seventh most prevalent cancer worldwide, poses a significant health challenge. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine, has exhibited promising inhibitory effects on the proliferation, invasion, and migration of various cancer cell types. Nevertheless, its specific impact and underlying mechanisms concerning HCC remain unclear. This research aimed to elucidate the anticancer properties and potential molecular mechanisms of acRoots in the HepG2 and LM3 cell lines. Our findings demonstrate that acRoots effectively hampers the in vitro proliferation, migration, and invasion of HCC cells. Furthermore, acRoots induces apoptosis and autophagy by impeding the AKT/mTOR signaling pathway, with its inhibitory effects on cells being restored under AKT activator induction. This study, for the first time, elucidates that acRoots can suppress HepG2 and LM3 cell proliferation by blocking the Akt/mTOR pathway, thereby activating apoptosis and autophagy. These results underscore the potential of acRoots as a promising antitumor agent for HCC.

Actinidia chinensis Planch Root extract suppresses the growth and metastasis of hypopharyngeal carcinoma by inhibiting E2F Transcription Factor 1-mediated MNX1 antisense RNA 1.

Increasing evidence has shown that traditional Chinese medicines and their bioactive components exert an anti-tumor effect, representing a novel treatment strategy. Actinidia chinensis Planch Root extracts (acRoots) have been reported to repress cancer cell proliferation and metastasis. The effect of acRoots on hypopharyngeal carcinoma progression was explored in this study. Firstly, data from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and colony formation assays showed that incubation with accRoots reduced cell proliferation of hypopharyngeal carcinoma cells. Moreover, acRoots promoted the cell apoptosis of hypopharyngeal carcinoma. Secondly, cell migration and invasion of hypopharyngeal carcinoma cells were suppressed by acRoots. Thirdly, E2F1 (E2F Transcription Factor 1) and lncRNA MNX1-AS1 (MNX1 antisense RNA 1) were up-regulated in hypopharyngeal carcinoma tissues, and reduced in hypopharyngeal carcinoma cells post acRoots incubation. Overexpression of E2F1 attenuated acRoots-induced decrease in MNX1-AS1 in hypopharyngeal carcinoma cells. Lastly, administration with acRoots retarded in vivo hypopharyngeal carcinoma growth through down-regulation of E2F1-mediated MNX1-AS1. In conclusion, acRoots exerted tumor-suppressive role in hypopharyngeal carcinoma through inhibition of E2F1-mediated MNX1-AS1.

Actinidia chinensis Planch. root extract inhibits the proliferation, migration and invasion of breast cancer cells via the AKT/GSK-3ß signaling pathway.

INTRODUCTION: Actinidia chinensis Planch. root extract (acRoots), known as a traditional Chinese medicine (TCM), has shown antitumor efficacy in various types of human cancers. However, its role and underlying mechanisms in breast cancer (BCa) have not been elucidated. MATERIAL AND METHODS: In the present study, the effects of acRoots on cell viability, apoptosis, migration and invasion were analyzed by MTT assay, colony formation, flow cytometry, wound healing and Transwell assay in MDA-MB-231 and MDA-MB-453 breast cancer cell lines. The expression levels of relevant proteins were determined by Western blot assay. RESULTS: The results revealed that acRoots inhibited proliferation, migration, and invasion and promoted apoptosis of BCa cells. Moreover, acRoots decreased the expression of cyclin D1, survivin, Bcl-2, N-cadherin, and Snail and increased the expression of Bax and E-cadherin in MDA-MB-231 and MDA-MB-453 cells. AcRoots inhibited the AKT/GSK-3b pathway by decreasing the levels of phosphorylated AKT, phosphorylated GSK-3b and b-catenin. CONCLUSIONS: The described effects of acRoots on the cultured BCa cells suggest that they may be mediated by the inhibition of the AKT/GSK-3b signaling pathway. Thus, further studies are warranted to test the possibility that AcRoots may be used as a promising anticancer agent for breast cancer treatment.

The bioactive ingredients in Actinidia chinensis Planch. Inhibit liver cancer by inducing apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia chinensis Planch. (ACP) is a common traditional Chinese medicine, which is mostly used for cancer treatment clinically. Liver cancer is a refractory tumor with a high incidence. Although ACP has been reported in the treatment of liver cancer, its possible mechanism of action is little known. AIM OF STUDY: The aim of this paper was to investigate the active components of ACP in the treatment of liver cancer and the related mechanisms by a network pharmacology approach. METHODS: The active components of ACP and the corresponding targets were obtained from multiple databases. Cytoscape software and STRING database were used to build the "herb-component-target (H-C-T)" network and protein-protein interactions (PPI) network. The key components and targets were further predicted by the Cytohubba plug-in in Cytoscape. Then, experiments were carried out on HepG2 cell line and Huh7 cell line to verify the effects and related mechanisms of the key compounds in ACP. RESULTS: 28 active components in ACP and 1299 related targets were screened out according to two indicators, oral bioavailability (OB) and drug-likeness (DL). The key compounds predicted include rutinum, astragalin, and L-epicatechin, and the main signaling pathways focus on apoptosis. Astragalin, a key compound in ACP, could inhibit the expression of Bcl-2, up-regulate the expression of Bax, cleaved caspase 3, cleaved caspase 8, and cleaved caspase 9, and regulate the apoptosis signaling pathway to inhibit the proliferation of liver cancer cells to play a therapeutic role in anti-liver cancer. CONCLUSIONS: These results suggest that ACP can alleviate the progression of liver cancer through the mechanisms predicted by network pharmacology, and provide a basis for the further understanding of the application of ACP in anti-cancer.

Actinidia chinensis Planch prevents proliferation and migration of gastric cancer associated with apoptosis, ferroptosis activation and mesenchymal phenotype suppression.

Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.

Actinidia Chinensis Planch Root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting the DLX2/TARBP2/JNK/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have confirmed that traditional Chinese herbs exert potential anti-tumor effects. Actinidia Chinensis Planch root has been used as a traditional Chinese medicine (TCM) for thousands of years. However, the mechanism of anti-tumor effects of Actinidia Chinensis Planch root has not been clearly clarified. AIM OF THE STUDY: To explore the molecular biological mechanisms underlying the inhibitory effect of Actinidia Chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In our previous study, we used mRNA chip analyses to identify genes regulated by acRoots. Further analyses of altered genes led to the identification of a key regulator of genes that responds to acRoots. We explored the effects of acRoots on the proliferation and invasion of HCC cells via cell counting as well as transwell assays, and further explored the molecular mechanisms underlying the effects of acRoots on HCC cells using qRT-PCR, western blot, and Chip-PCR. RESULTS: Increasing the concentration of acRoots as well as prolonging its action time enhanced the inhibitory activity of acRoots as well as its cytotoxicity against HCC cells. High TARBP2 expression in HCC cells, which is associated with advanced-stage HCC and poor prognoses in HCC patients, was downregulated by treatment with acRoots. Furthermore, acRoots inhibited proliferation, invasion, and epithelial-to-mesenchymal transition by downregulating TARBP2 expression. HCC cells with higher TARBP2 expression were more sensitive to acRoots. The expression of TARBP2 and DLX2 in HCC patients and HCC cell lines was significantly positively correlated, and DLX2 as a transcription factor may promote TARBP2 expression, thereby further activating the JNK/AKT signaling pathway leading to the inhibition of HCC. CONCLUSIONS: acRoots inhibited the malignant behavior of HCC cells by inhibiting TARBP2 expression, which is affected by the transcription factor DLX2, leading to a reduction in JNK/AKT signaling pathway activation.

Extraction Optimization, Physicochemical Characteristics, and Antioxidant Activities of Polysaccharides from Kiwifruit (Actinidia chinensis Planch.).

In order to evaluate effects of extraction techniques on the physicochemical characteristics and antioxidant activities of kiwifruit polysaccharides (KPS), and further explore KPS as functional food ingredients, both microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE) were optimized for the extraction of KPS. Furthermore, the physicochemical structures and antioxidant activities of KPS extracted by different techniques were investigated. The optimal extraction conditions of UAE and MAE for the extraction of KPS were obtained by response surface methodology. Different extraction techniques significantly affected the contents of uronic acids, molecular weights, molar ratios of constituent monosaccharides, and the degree of esterification of KPS. Results showed that KPS exhibited remarkable DPPH and ABTS radical scavenging activities, and reducing power. The high antioxidant activities observed in KPS extracted by the MAE method (KPS-M) might be partially attributed to its low molecular weight and high content of unmethylated galacturonic acid. Results suggested that the MAE method could be a good potential technique for the extraction of KPS with high antioxidant activity, and KPS could be further explored as functional food ingredients.

Actinidia chinensis Planch root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting epithelial-mesenchymal transition.

ETHNO-PHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated the potent anticancer activity of various Chinese herbs. Actinidia chinensis Planch root (acRoots), a traditional Chinese medicine, functions as an antitumor and detoxifying agent and plays a role in diuresis and hemostasis. Treatment with acRoots confers strong inhibition of tumor growth in various forms of cancer. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Our previous study used mRNA chip analyses to identify the genes regulated by acRoots. Further analyses of the altered genes identified a key regulator of genes in response to acRoots. Here, the effects of acRoots on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by cell counting, Transwell and apoptosis assays. In addition, the in vivo anti-HCC effects of acRoots were investigated using an HCC animal model. The expression of a key regulator of genes in response to acRoots was analyzed using quantitative polymerase chain reaction and western blotting. RESULTS: Treatment with acRoots (10 mg/mL) had no cytotoxicity in L02 cells and had a positive effect on L02 cell viability; however, it significantly inhibited HCC cell proliferation. Treatment with acRoots downregulated DLX2 gene expression in HCC cells, and high DLX2 expression was associated with advanced stage and poor prognosis in patients with HCC. Treatment with acRoots inhibited proliferation, invasion and migration, clonality, and the epithelial-to-mesenchymal transition, and promoted the apoptosis of HCC cells by downregulating DLX2 expression. HCC cells with higher DLX2 expression were more sensitive to acRoots. CONCLUSIONS: acRoots inhibited the malignant biological behavior of HCC cells via regulation of the epithelial-mesenchymal transition (EMT) by DLX2.

Rapid detection and characterization of major phenolic compounds in Radix Actinidia chinensis Planch by ultra-performance liquid chromatography tandem mass spectrometry.

Radix Actinidia chinensis Planch is a traditional Chinese herb, and its decotion had been widely used clinically to treat several types of cancer. In our study, the phenolic compounds constituting the major water soluble components of Radix A. chinensis were profiled and characterized by ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry. A total of 50 compounds were identified or tentatively characterized, including caffeic acid, p-coumaric acid, 29 catechin derivatives, 12 quinic acid derivatives and 7 coumarin derivatives. Most of the identified compounds were firstly reported from A. chinensis. Among them, scopoletin, scoplin, isofraxoside and quinic acid derivatives have not ever been reported from genus Actinidia previously. These phenolic compounds might be responsible for the antitumor activity of the water extract of radix A. chinensis, and the established analytical method could be applied to further study of quality evaluation and active components of Radix A. chinensis.

Anti-tumor activity of Actinidia chinensis planch / 中国药理学通报

Aim To evaluate the anti-tumor activity of the extract from the root of Actinidia chinensis planch in vitro and in vivo. Methods Active components from the root of Actinidia chinensis planch were isolated by traditional phytochemical techniques. The in vitro anti-tumor activity was determined by sulforhodamine B assay and the in vivo anti-tumor activity was evaluated using experimental mouse tumor models and human tumor xenografts in nude mice. Results Powdered air-dried roots of Actinidia chinensis planch were percolated with methanol at room temperature thrice. The filtrate was concentrated to dryness in vacuo and then was further extracted with ethyl acetate, n-butanol , and chloroform. The fraction extracted by chloroform displayed the most potent activity against several tumor cell lines including hepatocellular carcinoma Bel-7402 cells, non-small cell lung cancer A549 cells, lymphoma Ramos cells, and breast cancer MCF-7 cells. Further more, the anti-tumor efficacy of the chloroform fraction was confirmed in Bel-7402 xenografts in nude mice with the percentage inhibition of 38.0 %. Conclusion The extract of the root of Actinidia chinensis planch has anti-tumor activity, and the active components are mainly in the fraction extracted by chloroform.